15-88144779-T-C

Position:

• chr15-88144779-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012338.3(NTRK3):​c.464+2556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,070 control chromosomes in the GnomAD database, including 3,788 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3788 hom., cov: 32)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.93

Genes affected

NTRK3 (HGNC:8033): (neurotrophic receptor tyrosine kinase 3) This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation and may play a role in the development of proprioceptive neurons that sense body position. Mutations in this gene have been associated with medulloblastomas, secretory breast carcinomas and other cancers. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.464+2556A>G		intron_variant		ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.464+2556A>G		intron_variant		1	NM_001012338.3	ENSP00000485864

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32882 AN: 151952 Hom.: 3784 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32911 AN: 152070 Hom.: 3788 Cov.: 32 AF XY: 0.211 AC XY: 15722 AN XY: 74342

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.194

Alfa AF: 0.172 Hom.: 598

Bravo AF: 0.222

Asia WGS AF: 0.186 AC: 647 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.052
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3784405; hg19: chr15-88688010;